The core mission of this study is to define some of the processes involved in the initiation amd maintenance of high blood pressure. During previous years, we have identified vascular defects in the spontaneously hypertensive rat (SHR) and untreated human essential hyper-tensives. The most significant defect is a reduced arteriolar growth during the developmental phase of hypertension. Our long-term goal is to explore the possibility that the control of vessel growth is involved in the hypertension initiation or maintenance processes, and to investigate the mechanisms whereby this occurs. We propose to investigate the role of vessel growth in hypertension by performing four types of studies: 1) a temporal correlation of central hemodynamic variables measured in the unanesthetized SHR with the microvascular alterations occurring in the animal; 2) morphological and physiological investigations of venular growth prior to, during, and after the development of hypertension; 3) pharmacological studies of the ability of anti-hypertensive therapies to restore microvascular patterns in essential hypertensive patients; and 4) biochemical analyses of the regulation of vessel growth. These studies offer the potential for a better understanding of some of the basic mechanisms involved in the hypertensive process and since a sizable portion of this portion of this project is concerned with mechanism(s) regulating vascularization, the findings are of importance in the areas of collateralization of ischemic tissues, vascularization of tumors and aging.